Hydrochloric Acid → HCID 44548222, compound

HRID 1512898Notes

Reaction equation

HRID 1512898 reaction equation
C([O:3][C:4]([C@@H:6]1[CH2:8][C@H:7]1[C:9]1[C:17]2[C:12](=[C:13]([C:18]3[N:22]=[C:21]([C:23]4[CH:28]=[CH:27][C:26]([O:29][CH:30]([CH3:32])[CH3:31])=[C:25]([Cl:33])[CH:24]=4)[O:20][N:19]=3)[CH:14]=[CH:15][CH:16]=2)[N:11]([CH3:34])[CH:10]=1)=[O:5])C.[OH-].[Na+].Cl>C1COCC1>[Cl:33][C:25]1[CH:24]=[C:23]([C:21]2[O:20][N:19]=[C:18]([C:13]3[CH:14]=[CH:15][CH:16]=[C:17]4[C:12]=3[N:11]([CH3:34])[CH:10]=[C:9]4[C@@H:7]3[CH2:8][C@H:6]3[C:4]([OH:5])=[O:3])[N:22]=2)[CH:28]=[CH:27][C:26]=1[O:29][CH:30]([CH3:31])[CH3:32]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 58222469HCID 58222469, compound

Product 1

HCID 44548222HCID 44548222, compoundYield 21.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of trans-ethyl-2-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]cyclopropanecarboxylate (D64) (20 mg) in THF (5 mL) was added aqueous NaOH (2 M, 1 mL). The reaction was stirred at 60° C. for 4 h. The mixture was cooled to room temperature and acidified with aqueous HCl (2 M) to pH 4-5, partitioned between ethyl acetate (25 mL) and water (25 mL). The organic phase was washed with water (25 mL) and brine (25 mL), dried over anhydrous sodium sulphate and evaporated to give the crude product, which was purified by Mass Directed Auto Prep to afford trans-2-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]cyclopropanecarboxylic acid (E39) (4 mg). δH (DMSO-d6, 400 MHz): 1.31 (1H, m), 1.35 (6H, d), 1.42 (1H, m), 1.72 (1H, m), 2.48 (1H, m), 3.60 (3H, s), 4.88 (1H, m), 7.21 (2H, m), 7.45 (2H, m), 7.82 (1H, dd), 8.12 (1H, dd), 8.19 (1H, d), 12.27 (1H, br s). MS (ES): C24H22ClN3O4 requires 451; found 452.2 (M+H+).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. custompartitioned between ethyl acetate (25 mL) and water (25 mL)
  3. washThe organic phase was washed with water (25 mL) and brine (25 mL)
  4. dry with materialdried over anhydrous sodium sulphate
  5. customevaporated
  6. customto give the crude product, which
  7. customwas purified by Mass Directed Auto Prep

Sources & evidence

ORD record
ord-7cd3b86f753a44798ff0068e8ca3611f
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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